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Rectal CancerPhase 1/2NCT00226941

A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer

A Phase 1/2 study testing Cetuximab, Oxaliplatin and Capecitabine in people with Rectal Cancer and Colo-rectal Cancer, run by George Albert Fisher at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The objectives of this study are to: 1. To assess dose-limiting toxicities (DLTs) of capecitabine +/- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1) 2. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rectal Cancer, Colo-rectal Cancer
What is being tested?
Cetuximab, Oxaliplatin and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
Jun 2004to Feb 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically-confirmed adenocarcinoma of the rectum. Clinical stages T3; T4; or N1 as determined by endoscopic ultrasound; or a rectal CT or MRI scan are eligible, including T3 N0; T3 N1; T4 N0; T4 N1; T1-4 N1. Rectal cancers are defined as those whose distal border extends to within 12 cm of the anal verge.
  • Age ≥ 18
  • Karnofsky performance status (KPS) ≥ 70
  • Leukocyte count > 3,500 x 10e6/µL
  • Platelet count > 100,000/µL
  • Serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 x institutional upper limits of normal (ULN)
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  • Serum glutamic-pyruvic transaminase (SGPT) < 2.5 x ULN
  • Alkaline phosphatase < 2.5 x ULN
  • Total bilirubin < 1.5x ULN
  • Creatinine:
  • Within normal institutional limits
  • OR
  • Creatinine clearance > 60 mL/min/1.73 m2 (if serum creatinine levels above institutional normal)
  • Ability to swallow pills without difficulty
  • Women of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG), within 72 hours prior to the start of study medication
  • Women of child-bearing potential must be using an adequate method of contraception to avoid pregnancy throughout the treatment

Who cannot join

  • Metastatic (M1) or stage IV disease
  • Prior history of treatment with cetuximab or other therapy targeting EGFR
  • Prior history of anti-cancer murine monoclonal antibody therapy
  • Prior pelvic or whole abdominal radiotherapy
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
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  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness / social situations that would limit compliance with study requirements
  • Patients with a concurrent malignancy or previous malignancy within 5 years of screening will be excluded from this study (EXCEPTION: concurrent or previous non-melanoma skin cancer, hematolymphoid malignancy or carcinoma in-situ of the cervix may be allowed at the investigator's discretion)
  • Inability to sign written consent
  • Pregnant or breastfeeding
  • Unwilling or unable to use effective contraception in self or partner for the entire study period and for up to 4 weeks after the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgical Resection for Locally-Advanced Rectal Cancer

The objectives of this study are to:

  1. To assess dose-limiting toxicities (DLTs) of capecitabine +/- oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
  2. To determine the maximum-tolerated dose (MTD) when capecitabine
  • oxaliplatin in a combination regimen with capecitabine and radiotherapy (Phase 1)
  1. To determine the pathologic response rate of cetuximab +/- oxaliplatin in combination with capecitabine and radiotherapy (Phase 2)
Read the detailed description

Part of the treatment plan for this study is surgical removal of the tumor that is planned to occur 6 to 8 weeks after completion of radiotherapy (XRT). This study consists of 2 distinct phases (Phase 1 and Phase 2).

In Phase 1, the objectives are to

  1. Assess dose-limiting toxicities (DLTs) and
  2. Determine a maximum-tolerated dose (MTD)

The Phase 1 endpoints are assessed on an initial cohort of patients after the completion of the chemo-radiotherapy regimen at defined timepoints that precede surgery.

Phase 2 is the efficacy assessment portion of this study. In Phase 2, the objective is to accrue an expansion cohort. Efficacy assessments for phase 2 are to be assessed across all study participants at the time of, or after, surgery, as measured by the pathologic response rate; downstaging; and survival at 5 years from the start of treatment.

Being tested
Cetuximab, Oxaliplatin, Capecitabine, Radiotherapy, Diphenhydramine hydrochloride (HCl)
Medical subject headings
Rectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabDrug

    Also called Erbitux, C225, IMC-C225

    Cetuximab is a chimeric anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, administered via a intravenous (IV) infusion at 400 mg/m² (initial loading dose) or 250 mg/m² (weekly dose). Dosage is based on m² of body surface area (BSA)

  • OxaliplatinDrug

    Also called Eloxatin

    Oxaliplatin is a cancer medication used to treat colorectal cancer, and is administered on Days 2 and 23.

  • CapecitabineDrug

    Also called Xeloda

    Capecitabine is a cancer medication, and is administered based on m² of body surface area (BSA) delivered in equivalent morning and evening doses

  • RadiotherapyRadiation

    Also called XRT

    Radiotherapy is administered on weekdays in 180 centigray fractions ("doses"), for 28 total fractions delivering a total dose of 5040 centigray (cGy)

  • Diphenhydramine hydrochloride (HCl)Drug

    Also called Benadryl, Unisom, Sominex

    Diphenhydramine HCl 50 mg (or equivalent) is administered as a per-medication for cetuximab

Study groups in NCT00226941
Study groupRoleWhat they receive
Group 1 - Cetuximab + Capecitabine-800 + XRT + Oxaliplatin-100Experimental* Cetuximab 250 mg/m² / week * Capecitabine 800 mg/m² * Radiotherapy (XRT) * Oxaliplatin 100 mg/m², Days 2 and 23
Receives: Drug: Cetuximab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)
Group 2 - Cetuximab + Capecitabine-700 + XRT + Oxaliplatin-85Experimental* Cetuximab 250 mg/m² / week * Capecitabine 700 mg/m² * Radiotherapy (XRT) * Oxaliplatin 85 mg/m², Days 2 and 23
Receives: Drug: Cetuximab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)
Group A - Cetuximab + Capecitabine-800 + XRTExperimental* Cetuximab 250 mg/m² / week * Capecitabine 800 mg/m² * Radiotherapy (XRT)
Receives: Drug: Cetuximab; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)
Group B - Cetuximab + Capecitabine-1000 + XRTExperimental* Cetuximab 250 mg/m² / week * Capecitabine 1000 mg/m² * Radiotherapy (XRT)
Receives: Drug: Cetuximab; Drug: Capecitabine; Radiation: Radiotherapy; Drug: Diphenhydramine hydrochloride (HCl)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting Toxicity (DLT) - Number of DLTs by Treatment Group

    Dose-limiting Toxicity (DLT) is the measure used to establish overall Maximum-tolerated dose (MTD) of cetuximab + capecitabine + radiotherapy +/- oxaliplatin. MTD is defined as the highest dose level for which participants have a < 30% incidence of dose-limiting toxicity (DLT). The outcome is expressed as the number of DLTs by treatment group.

    Measured: 10 weeks

  2. Dose-limiting Toxicity (DLT) - Number of Participants Affected

    Dose-limiting Toxicity (DLT) is the measure used to establish overall Maximum-tolerated dose (MTD) of cetuximab + capecitabine + radiotherapy +/- oxaliplatin. MTD is defined as the highest dose level for which participants have a < 30% incidence of dose-limiting toxicity (DLT). The outcome is expressed as the number of participants experiencing a DLT.

    Measured: 10 weeks

Secondary outcomes (5)

  1. Pathologic Response Rate

    After treatment with capecitabine, cetuximab, radiotherapy, and oxaliplatin, the pathologic response rate was assessed based on the excised tumor taken at the time of surgical resection. Pathologic response rate was determined as the number and proportion of participants who experienced either downstaging of their disease, or complete response (CR, no detectable disease). A participant will be considered to have downstaging of the tumor as a result of the neoadjuvant therapy when the primary tumor (T) stage by pathology isless than the T stage by clinical (endoscopic) evaluation, or when the regional lymph node (N) tumor stage by pathology is less than the N stage by clinical (endoscopic) evaluation.

    Measured: 12 to 14 weeks after radiotherapy

  2. Tumor Downstaging at Surgical Resection

    Downstaging means a reduction from the stage of disease observed at baseline to the stage of disease after treatment with cetuximab, radiotherapy, oxaliplatin, and capecitabine, as determined at the time of surgical removal of the tumor. Downstaging may be observed as improvements in tumor staging at the primary site of the tumor; in nearby (regional) lymph nodes; or in metastatic disease beyond the regional lymph nodes. This outcome specifically does not include participants that achieved a complete response, nor those that experienced no response or disease progression.

    Measured: 12 to 14 weeks after radiotherapy

  3. Time-to-Progression (TTP)

    Time-to-progression was assessed as the time from the date of surgical resection to the appearance of either local disease recurrence or distant metastases by any modality (eg, clinical exam, endoscopy, radiographic imaging). All relapses were to be confirmed by biopsy and pathology review.

    Measured: 5 years

  4. Overall Survival (OS)

    Overall Survival (OS) was assessed as the mean survival from the date of entry on study though 72 months.

    Measured: 72 months

  5. Survival at 5 Years

    Survival at 5 years was assessed as the number of participants alive 5 years after starting treatment.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2005 (estimated)
  2. Study startJun 2004
  3. Primary completionMar 2008
  4. Study completionFeb 2009

Why it stopped: The response rate observed in the phase 1 portion of the study did not merit further evaluation in phase 2 portion of the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Sequential design for 4 dose combinations (arms) through phase 1
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00226941
Sponsor's protocol ID
IRB-12426
Other IDs
COR0001, 95054
Status last verified
Nov 2017
First submitted
8 Sep 2005
Last updated
8 Dec 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab, Oxaliplatin and Capecitabine in people with Rectal Cancer and Colo-rectal Cancer, run by George Albert Fisher at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicity (DLT) - Number of DLTs by Treatment Group (time frame: 10 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00226941.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2017.

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